This invention relates to a novel process for the preparation of organic halogen compounds whose halogen atom is radioactive from inactive organic halogen compounds by halogen exchange.
Radioactive-labeled halogen compounds are of great interest, since numerous radioactive diagnostic agents contain a radioactive halogen, especially iodine. Of great significance are thyroxine-I.sup.131 for thyroid diagnostics, sodium diatrizoate-I.sup.131 for testing the kidney function, the sodium salt of tetrachlorotetraiodofluorescein-I.sup.131 for testing the liver function, bromthalein-I.sup.131 for gall bladder diagnostics, N,N'-hydroxydiacetyl-bis(3-methylamino-2,4,6-triiodobenzoic acid)-I.sup.131 and N,N'-adipoylbis(3-amino-2,4,6-triiodobenzoic acid)-I.sup.131 for diagnostic purposes in connection with the liver and gall bladder.
The heretofore known processes for the production of labeled halogen compounds are not universally satisfactory.
In "Nature" 184 (1959), 913, a thermal halogen exchange in an aqueous solution is disclosed. This process is limited to certain specific, water-soluble organic compounds. For example, in this process radioactive iodine can be exchanged in Compound I below, but not in Compounds II and III, although the latter compounds are also water-soluble. ##SPC1##
Moreover, the process described in "Nature" has the disadvantage in practical handling, e.g., in isolation of very small quantities. Moreover difficulties are encountered when producing specifically highly tagged compounds, which are required for scintigraphy.
In several cases, a halogen exchange can also be accomplished on chromatographic columns. However, apart from a limited field of application, these processes are very complicated and time-consuming and disadvantageous with respect to the existing regulations relating to radioprotection.
German Published Application DAS 1,244,185 describes a process for the preparation of carrier-free, iodine-labeled organic compounds in which the halogen compound is exposed, in the presence of carrier-free iodine-131, to the radiation field of a nuclear reactor. However, this method is not feasible in practice, which requires a rapid halogen exchange without simultaneous destruction of the compound to be labeled.
In the synthesis of halogen-tagged organic compounds, conventional methods are generally employed, employing a radio-active precursor compound. Frequently, however, additional techniques must be utilized and/or additional stages must be incorporated in these methods in order to obtain the labeled compounds. For example, in the production of iodine-tagged tetraiodophthalic acid morpholide, it was necessary to develop a special apparatus (Acta Chem. Scand. 15 (1962), 1139-1142).
In contrast thereto, the novel process of this invention for the preparation of organic radiohalogen compounds is generally applicable to the production of compounds having a wide variety of structures, takes place under gentle conditions, and requires little time.